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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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NBL1
NBL1, DAN family BMP antagonist
Chromosome 1 · 1p36.13
NCBI Gene: 4681Ensembl: ENSG00000158747.15HGNC: HGNC:7650UniProt: A0A087WTY6
34PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
identical protein bindingGO:0005615negative regulation of BMP signaling pathwayprotein bindingnontoxic goiterAbnormality of the skeletal systemmultinodular goiterHashimoto's thyroiditis
✦AI Summary

NBL1 (Noggin-like, DAN family BMP antagonist) is a secreted protein that functions as a negative regulator of bone morphogenetic protein (BMP) signaling. NBL1 specifically antagonizes BMP2 and BMP4 signaling through receptor ligand activity, forming noncovalently linked homodimers that are generated in a cell-type-specific manner 1. The protein is involved in nervous system development, neuron differentiation, and morphogenesis [GO annotations], with its gene located at chromosome 1.11-p36.13, a region linked to neuroblastoma genesis and progression 2. Mechanistically, NBL1 inhibits both canonical (phospho-Smad1/5) and non-canonical (phospho-p38) BMP signaling pathways 3. NBL1 expression is regulated by gonadotropins and oocyte-derived factors like GDF9, suggesting roles in folliculogenesis and reproductive biology 1. Recent studies demonstrate NBL1's anti-fibrotic and anti-scarring properties; corneal treatment with NBL1 facilitated wound re-epithelialization and significantly reduced fibrosis without immune suppression 3. In disease contexts, NBL1 functions as a tumor suppressor. Hypermethylation of the NBL1 gene in ovarian cancer correlates with reduced mRNA expression and lower tumor suppressor function 4. In esophageal cancer, miR-1301-3p promotes invasion, migration, and EMT progression by downregulating NBL1 expression, with low NBL1 levels associated with poor prognosis 5. Additionally, NBL1 upregulation in mesenchymal stem cell-derived exosomes inhibits hypoxia-induced pulmonary vascular remodeling by modulating TGF-β1/Smad2/3 signaling 6.

Sources cited
1
NBL1 specifically antagonizes BMP2 and BMP4 signaling, forms noncovalently linked homodimers, and is regulated by gonadotropins and GDF9 in ovarian granulosa cells
PMID: 22357543
2
NBL1 reduces corneal fibrosis and scar formation by inhibiting both canonical Smad1/5 and non-canonical p38 BMP signaling pathways
PMID: 38002252
3
NBL1 (DAN) is a 27-kD secreted protein whose gene is located at 1p36.11-p36.13, a region linked to neuroblastoma genesis and progression; aberrant bands detected in neuroblastoma cases
PMID: 9309143
4
NBL1 gene hypermethylation in ovarian cancer is associated with reduced mRNA expression and functions as a tumor suppressor
PMID: 40722077
5
miR-1301-3p promotes esophageal cancer invasion, migration, and EMT by downregulating NBL1; low NBL1 expression associates with poor prognosis
PMID: 37680006
6
NBL1 upregulation in mesenchymal stem cell-derived exosomes inhibits hypoxia-induced pulmonary vascular remodeling via TGF-β1/Smad2/3 pathway modulation
PMID: 38717187
Disease Associationsⓘ20
nontoxic goiterOpen Targets
0.45Moderate
Abnormality of the skeletal systemOpen Targets
0.41Moderate
multinodular goiterOpen Targets
0.35Weak
Hashimoto's thyroiditisOpen Targets
0.30Weak
obesityOpen Targets
0.29Weak
hypothyroidismOpen Targets
0.12Weak
obstructive sleep apneaOpen Targets
0.08Suggestive
coronary artery diseaseOpen Targets
0.07Suggestive
bipolar I disorderOpen Targets
0.06Suggestive
cancerOpen Targets
0.05Suggestive
small cell lung carcinomaOpen Targets
0.04Suggestive
neoplasmOpen Targets
0.04Suggestive
aortic diseaseOpen Targets
0.04Suggestive
diabetic nephropathyOpen Targets
0.04Suggestive
ThyrotoxicosisOpen Targets
0.04Suggestive
ovarian cancerOpen Targets
0.03Suggestive
thyroid diseaseOpen Targets
0.03Suggestive
goiterOpen Targets
0.03Suggestive
autoimmune diseaseOpen Targets
0.03Suggestive
infectionOpen Targets
0.03Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
GDF5Protein interaction92%BMP2Protein interaction92%BMP4Protein interaction92%BMP6Protein interaction92%BMP7Protein interaction92%AMHProtein interaction91%
Tissue Expression6 tissues
Ovary
100%
Heart
27%
Lung
23%
Brain
10%
Bone Marrow
7%
Liver
1%
Gene Interaction Network
Click a node to explore
NBL1GDF5BMP2BMP4BMP6BMP7AMH
PROTEIN STRUCTURE
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AlphaFoldAI-predicted · UniProt P41271
View on AlphaFold ↗
RankingsWhere NBL1 stands among ~20K protein-coding genes
  • #11,192of 20,598
    Most Researched34
Genes detectedNBL1
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Interleukin 2 with anti-GD2 antibody ch14.18/CHO (dinutuximab beta) in patients with high-risk neuroblastoma (HR-NBL1/SIOPEN): a multicentre, randomised, phase 3 trial.
PMID: 30442501
Lancet Oncol · 2018
1.00
2
NBL1 Reduces Corneal Fibrosis and Scar Formation after Wounding.
PMID: 38002252
Biomolecules · 2023
0.90
3
Randomized Trial of Two Induction Therapy Regimens for High-Risk Neuroblastoma: HR-NBL1.5 International Society of Pediatric Oncology European Neuroblastoma Group Study.
PMID: 34152804
J Clin Oncol · 2021
0.80
4
[DAN gene].
PMID: 9309143
Gan To Kagaku Ryoho · 1997
0.70
5
ctDNA methylation profiling reveals NBL1 as a promising biomarker for early ovarian cancer screening.
PMID: 40722077
World J Surg Oncol · 2025
0.60